Trypanosoma (Schizotrypanum) dionisii as a model for chemotherapeutic studies related to Chagas's disease.
Cultivated trypomastigotes of Trypanosoma (Schizotrypanum) dionisii were added to cultures of buffalo lung (BL) cells at 37 degrees C in a ratio of 500 parasites per cell. More than 60% of the cells became infected with amastigotes and the system was used to test trypanosomicidal activity and cytotoxicity of possible chemotherapeutic agents for use in Chagas's disease. Three nitroheterocyclic compounds known to be active against T. cruzi in cell cultures (nifurtimox, benznidazole and SQ 18506) were active at similar levels against intracellular T. dionisii (1, 10 and 0.1 microgram ml-1 respectively); concentrations of 10, 10 and 1 microgram ml-1 respectively were cytotoxic. Other substances, not regarded as active against T. cruzi (metronidazole, pentamidine and pentostam, had little or no trypanosomicidal effect even at 100 microgram ml-1. A recently developed nitroheterocyclic compound (MK 436) was active, and not cytotoxic, at 10 microgram ml-1 and possibly warrants further investigation Tetraethylthiuram disulphide, an inhibitor of threonine dehydrogenase which prevents growth of extracellular T. cruzi and T. dionisii in vitro at 1 microgram ml-1, was only slightly trypanosomicidal to intracellular T. dionisii at this dose; it was also somewhat cytotoxic.
D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D013045:Species Specificity; D014345:Trypanosoma / Q000187:drug effects*; D014349:Trypanosoma cruzi / Q000187:drug effects